Advanced Molecular Genetics-Biology 566 Phosphorylation and dephosphorylation - Regulation in the downstream signaling cascade
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Dephosphorylation by phosphatases

Like the Kinases, Phosphatases are divided into two general groups, tyrosine phosphatases and serine/threonine phosphatases.

The tyrosine phosphatases can be further subdivided into receptor/membrane associated and cytoplasmic.

The tyrosine phosphatases are single subunit proteins with specificities determined by the phosphatase itself, while serine/threonine phosphatases are oligomers whose specificity is usually determined by the associated protein.

Here are two examples of phosphatases that provide the balancing switch to reverse the effects of a protein kinase. The first example regulates the release of glucose from glycogen and the second example regulates the T-cell receptor response.

There are a number of domains associated with cytosolic and membrane associated phosphatases.

The role of Protein Tyrosine Phosphatases (PTPs) in signal transduction

Positive regulation

SHP-2 Domains (Src Homology Phosphatase-2)

Negative regulation through dephosphorylation

MKP-1 (Map Kinase Phosphatase -1)

Serum activates signal transduction to nucleus where expression of several genes are activated. One of those genes is MKP-1, whose gene products appear about 20 minutes after the addition of serum. MKP-1 is stabilized by the ERK kinase which is also the substrate for dephosphorylation by MKP-1.

SHP-1 was discovered in mice with a moth-eaten appearance that was the result of an autoimmune condition caused by the down regulation of signal transduction pathways related to the proliferation and differentiation of haemapoietic cells.

EPO-R has no cytoplasmic tyrosine kinase domain but must recruit this activity by associating with the JAK protein.

Questions:

What is the impact on growth of cells if a phosphatase, that we have spoken of above, is inactivated?

Can overproduction of phosphatases act as tumor suppressors?

PTEN a phosphatase for phosphoproteins and phospholipids.

PTEN does operate as a tumor suppressor.

Serine-threonine phosphatases

Serine/threonine phosphatases are bound by modulator proteins that aid in the localization of these generalized phosphatases and prevent generalized dephosphorylation.